I am using GAE to host several high-traffic applications. Like on the order of 50-100 req/sec. It is great, I can't recommend it enough.
My previous experience with web development was with Ruby (Rails/Merb). Learning Python was easy. I didn't mess with Django or Pylons or any other framework, just started from the GAE examples and built what I needed out of the basic webapp libraries that are provided.
If you're used to the flexibility of SQL the datastore can take some getting used to. Nothing too traumatic! The biggest adjustment is moving away from JOINs. You have to shed the idea that normalizing is crucial.
Ben
